title: Acceleration of bone development and regeneration through the Wnt/β-catenin signaling pathway in mice heterozygously deficient for GSK-3β.
abstract: Glycogen synthase kinase (GSK)-3β plays an important role in osteoblastogenesis by regulating the Wnt/β-catenin signaling pathway. Therefore, we investigated whether GSK-3β deficiency affects bone development and regeneration using mice heterozygously deficient for GSK-3β (GSK-3β(+/-)). The amounts of β-catenin, c-Myc, cyclin D1, and runt-related transcription factor-2 (Runx2) in the bone marrow cells of GSK-3β(+/-) mice were significantly increased compared with those of wild-type mice, indicating that Wnt/β-catenin signals were enhanced in GSK-3β(+/-) mice. Microcomputed tomography of the distal femoral metaphyses demonstrated that the volumes of both the cortical and trabecular bones were increased in GSK-3β(+/-) mice compared with those in wild-type mice. Subsequently, to investigate the effect of GSK-3β deficiency on bone regeneration, we established a partial bone defect in the femur and observed new bone at 14 days after surgery. The volume and mineral density of the new bone were significantly higher in GSK-3β(+/-) mice than those in wild-type mice. These results suggest that bone formation and regeneration in vivo are accelerated by inhibition of GSK-3β, probably through activation of the Wnt/β-catenin signaling pathway.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Arioka
authors.forename: Fumi
authors.initials: F
authors.lastname: Takahashi-Yanaga
authors.forename: Masanori
authors.initials: M
authors.lastname: Sasaki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yoshihara
authors.forename: Sachio
authors.initials: S
authors.lastname: Morimoto
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takashima
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Mori
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sasaguri
mesh_terms: D000818:Animals; D001846:Bone Development; D001861:Bone Regeneration; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; C493726:Runx1 protein, mouse; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1; D038362:Glycogen Synthase Kinase 3
keywords: Bone regeneration; GSK-3β; Wnt/β-catenin signaling pathway